Latest Articles from BioDiscovery Latest 2 Articles from BioDiscovery https://biodiscovery.pensoft.net/ Thu, 28 Mar 2024 12:03:28 +0200 Pensoft FeedCreator https://biodiscovery.pensoft.net/i/logo.jpg Latest Articles from BioDiscovery https://biodiscovery.pensoft.net/ Perivascular adipose tissue as regulator of the force of artery contractions in health and disease https://biodiscovery.pensoft.net/article/19831/ BioDiscovery 20: e19831

DOI: 10.3897/biodiscovery.20.e19831

Authors: Hristo Gagov, Radoslava Emilova, Daniela Dimitrova, Mitko Mladenov, Rudolf Schubert

Abstract: During the last two decades, perivascular adipose tissue (PVAT) has been revealed as an important regulator of vascular processes such as proliferation of smooth muscle cells, pro- and anti-oxidant reactions in the vascular wall, angiogenesis, inflammation, apoptosis of neutrophils, migration of monocytes and others. PVAT derived mediators either increase or decrease the amplitudes of the force of artery contraction measured using isometric small vessel myography. In healthy animals and humans predominates the relaxing effect while in diseases the contractile influence of PVAT is common. In aging and pathological conditions like atherosclerosis and diabetes, or with environmental factors like tobacco smoke and high-fat diet, the phenotype of perivascular adipocytes is changed from anti-inflammatory to pro-inflammatory. This change is accompanied by a significant rearrangement of mediators released from PVAT.

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Conference Abstract Tue, 1 Aug 2017 16:21:23 +0300
Drug resistance of cancer cells is crucially affected by expression levels of ABC-transporters https://biodiscovery.pensoft.net/article/11211/ BioDiscovery 20: e11211

DOI: 10.3897/biodiscovery.20.e11211

Authors: Petr Mlejnek, Petr Dolezel, Eliska Ruzickova

Abstract: Dasatinib (DAS), a second generation of tyrosine kinase inhibitor (TKI), represents excellent choice for the treatment of chronic myeloid leukemia resistant to imatinib. Unfortunately, recent laboratory studies suggested that antiproliferative effect of DAS might be significantly reduced due to the overexpression of the ATP-binding cassette (ABC) transporters, ABCB1 and ABCG2. However, whether these drug transporters might compromise therapeutic effect of DAS in clinic is unclear. We believe that the drug transporter expression level is a crucial factor that affects the results and its consideration may help to explain the existing controversy. In addition, clinically relevant concentrations of drug must be used. In our study, human leukemia K562 cells with high and low expression levels of ABCB1 or ABCG2 were used. DAS was applied at nanomolar concentrations. We observed that K562 cells expressing high levels of ABCB1 and ABCG2 contained significantly reduced intracellular levels of DAS and these cells exhibited significantly increased resistance to this drug. Importantly, cells with the low expression of ABCB1 or ABCG2 effluxed DAS less efficiently, however, still significantly. Accordingly, the observed resistance was lower but significant. Conclusions: The antiproliferative effects of DAS might be reduced by ABCB1 or ABCG2. However, the actual effect of these ABC transporters on DAS efficiency depends on their expression levels. The lower expression levels of ABC transporters mediate lower resistance. Considering the fact that expression levels of ABCB1 and ABCG2 transporters are usually low in clinical samples, their contribution to the overall resistance to DAS is probably low but significant.

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Research Article Wed, 8 Feb 2017 10:52:09 +0200